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Aid translocation

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https://www.readbyqxmd.com/read/28199309/phosphatidylinositol-3-kinase-%C3%AE-blockade-increases-genomic-instability-in-b-cells
#1
Mara Compagno, Qi Wang, Chiara Pighi, Taek-Chin Cheong, Fei-Long Meng, Teresa Poggio, Leng-Siew Yeap, Elif Karaca, Rafael B Blasco, Fernanda Langellotto, Chiara Ambrogio, Claudia Voena, Adrian Wiestner, Siddha N Kasar, Jennifer R Brown, Jing Sun, Catherine J Wu, Monica Gostissa, Frederick W Alt, Roberto Chiarle
Activation-induced cytidine deaminase (AID) is a B-cell-specific enzyme that targets immunoglobulin genes to initiate class switch recombination and somatic hypermutation. In addition, through off-target activity, AID has a much broader effect on genomic instability by initiating oncogenic chromosomal translocations and mutations involved in the development and progression of lymphoma. AID expression is tightly regulated in B cells and its overexpression leads to enhanced genomic instability and lymphoma formation...
February 15, 2017: Nature
https://www.readbyqxmd.com/read/28192748/exposure-to-pm2-5-induces-aberrant-activation-of-nf-%C3%AE%C2%BAb-in-human-airway-epithelial-cells-by-downregulating-mir-331-expression
#2
Lei Song, Dan Li, Xiaoping Li, Lianjun Ma, Xiaoxue Bai, Zhongmei Wen, Xiufang Zhang, Dong Chen, Liping Peng
Exposure to particulate matter (PM) with an aerodynamic diameter≤2.5μm (PM2.5) induces reactive oxygen species (ROS) and pro-inflammatory cytokine production, leading to airway epithelial injury. However, the mechanisms underlying the toxicity of PM2.5 have not been clarified. Here, we show that exposure to PM2.5 induces sustained activation of the nuclear factor kappa B (NF-κB) signaling in human airway epithelial Beas-2B (B2B) cells. In addition, PM2.5 exposure significantly decreased miR-331 expression in B2B cells, which was abrogated by inhibition of ROS or phosphoinositide 3-kinase (PI3K)/Akt pathway...
February 6, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28188246/cutting-edge-the-transcription-factor-sox2-regulates-aid-expression-in-class-switched-b-cells
#3
Lauren J DiMenna, Wei-Feng Yen, Laura Nicolas, Rahul Sharma, Zara N Saldanha, Jayanta Chaudhuri
IgH class switch recombination (CSR) occurs through the deliberate introduction of activation-induced cytidine deaminase (AID)-instigated DNA double-strand breaks into the IgH loci. Because double-strand breaks are generally highly toxic, mechanisms that regulate AID expression are of much relevance to CSR and genomic integrity; however, effectors of such regulatory processes are still poorly understood. In this article, we show that the transcription factor sex determining region Y-box 2 (Sox2) is expressed in activated B cells, but almost exclusively in those that have undergone CSR...
February 10, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28176781/rad52-competes-with-ku70-ku86-for-binding-to-s-region-dsb-ends-to-modulate-antibody-class-switch-dna-recombination
#4
Hong Zan, Connie Tat, Zhifang Qiu, Julia R Taylor, Justin A Guerrero, Tian Shen, Paolo Casali
Antibody class-switch DNA recombination (CSR) is initiated by AID-introduced DSBs in the switch (S) regions targeted for recombination, as effected by Ku70/Ku86-mediated NHEJ. Ku-deficient B cells, however, undergo (reduced) CSR through an alternative(A)-NHEJ pathway, which introduces microhomologies in S-S junctions. As microhomology-mediated end-joining requires annealing of single-strand DNA ends, we addressed the contribution of single-strand annealing factors HR Rad52 and translesion DNA polymerase θ to CSR...
February 8, 2017: Nature Communications
https://www.readbyqxmd.com/read/28169073/partition-uptake-of-a-brominated-diphenyl-ether-by-the-edible-plant-root-of-white-radish-raphanus-sativus-l
#5
Chien-Ying Yang, Meei-Ling Chang, Siang Chen Wu, Yang-Hsin Shih
Polybrominated diphenyl ethers (PBDEs) are of a class of emerging contaminants. In this study, the accumulation of 4-bromodiphenyl ether (BDE-3) by different parts of a live white radish was investigated. Different cultural media (hydroponics, silica sand, and soil) were used to sustain the radish plant during its uptake and in-plant translocation of BDE-3. The results showed that BDE-3 can be translocated from the roots to the aboveground organs and the accumulated levels of BDE-3 in different parts of the white radish followed the order for the three types of cultivation: fibrous roots > peels > main roots > leaves...
February 3, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28140477/coexistence-of-fusion-and-concrescence-of-primary-teeth-in-a-child-with-down-syndrome
#6
Akshara Singh, Hind Pal Bhatia, Naresh Sharma
Down syndrome is one of the most common congenital anomaly. It is most frequently caused by trisomy of chromosome 21. Other causes can be mosaicism and translocation. Such patients are commonly encountered in routine dental practice. This syndrome has wide range of medical and dental abnormalities. This paper presents a unique case of fusion and concrescence of retained primary teeth in a child with Down syndrome. The incidence of such anomalies is quite low in these cases. Thus, a better awareness of such conditions on part of a dental practitioner will aid in the provision of enhanced dental care to these patients...
January 31, 2017: Special Care in Dentistry
https://www.readbyqxmd.com/read/28137224/sulfated-glycans-in-hiv-infection-and-therapy
#7
Vitor H Pomin, Francisco F Bezerra, Paulo A G Soares
The human immunodeficiency virus (HIV) is the infectious agent causative of the acquired immune deficiency syndrome (AIDS). The number of HIV-infected people in the globe is incredibly large. Contrary to the big contamination rates, the incidence recently reported to AIDS-related deaths are fairly lower, less than 5 % of the total infected population. The reduced rates of the AIDS-associated deaths rely primarily on the growing availability, variety and efficiency of the antiretroviral treatments. During the initial molecular events of the HIV infectivity, the glycoprotein gp120 on the HIV envelop must interact with CD4 and heparan sulfate (HS) proteoglycans on the surface of the host cells in order to enable HIV attachment, fusion and entry into these cells...
January 27, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28134625/autophagy-facilitates-macrophage-depots-of-sustained-release-nanoformulated-antiretroviral-drugs
#8
Divya Prakash Gnanadhas, Prasanta K Dash, Brady Sillman, Aditya N Bade, Zhiyi Lin, Diana L Palandri, Nagsen Gautam, Yazen Alnouti, Harris A Gelbard, JoEllyn McMillan, R Lee Mosley, Benson Edagwa, Howard E Gendelman, Santhi Gorantla
Long-acting anti-HIV products can substantively change the standard of care for patients with HIV/AIDS. To this end, hydrophobic antiretroviral drugs (ARVs) were recently developed for parenteral administration at monthly or longer intervals. While shorter-acting hydrophilic drugs can be made into nanocarrier-encased prodrugs, the nanocarrier encasement must be boosted to establish long-acting ARV depots. The mixed-lineage kinase 3 (MLK-3) inhibitor URMC-099 provides this function by affecting autophagy. Here, we have shown that URMC-099 facilitates ARV sequestration and its antiretroviral responses by promoting the nuclear translocation of the transcription factor EB (TFEB)...
January 30, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28121054/enhanced-aerobic-glycolysis-by-s-nitrosoglutathione-via-hif-1%C3%AE-associated-glut1-aldolase-a-axis-in-human-endothelial-cells
#9
Jieping Yan, Xin Huang, Danyan Zhu, Yijia Lou
S-nitrosoglutathione (GSNO)-induced apoptosis is associated with reactive oxygen species and loss of mitochondrial Omi/HtrA2 in human endothelial cells (ECs). But its upstream regulation is still not elucidated. Here, we demonstrate that hypoxia induced factor-1α (HIF-1α)-linked aerobic glycolysis is associated with mitochondrial abnormality by treatment of human EC-derived EA.hy926 cells with GSNO (500 µM) for 6 h. GSNO exposure increased the levels of Aldolase A and glucose transporter-1 (GLUT1) mRNAs and proteins...
January 25, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28088889/-spontaneous-bacterial-peritonitis
#10
Bálint Velkey, Eszter Vitális, Zsuzsanna Vitális
Spontaneous bacterial peritonitis occurs most commonly in cirrhotic patients with ascites. Pathogens get into the circulation by intestinal translocation and colonize in peritoneal fluid. Diagnosis of spontaneous bacterial peritonitis is based on elevated polymorphonuclear leukocyte count in the ascites (>0,25 G/L). Ascites culture is often negative but aids to get information about antibiotic sensitivity in positive cases. Treatment in stable patient can be intravenous then orally administrated ciprofloxacin or amoxicillin/clavulanic acid, while in severe cases intravenous III...
January 2017: Orvosi Hetilap
https://www.readbyqxmd.com/read/28088785/the-igh-locus-3-cis-regulatory-super-enhancer-co-opts-aid-for-allelic-transvection
#11
Sandrine Le Noir, Brice Laffleur, Claire Carrion, Armand Garot, Sandrine Lecardeur, Eric Pinaud, Yves Denizot, Jane Skok, Michel Cogné
Immunoglobulin heavy chain (IgH) alleles have ambivalent relationships: they feature both allelic exclusion, ensuring monoallelic expression of a single immunoglobulin (Ig) allele, and frequent inter-allelic class-switch recombination (CSR) reassembling genes from both alleles. The IgH locus 3' regulatory region (3'RR) includes several transcriptional cis-enhancers promoting activation-induced cytidine deaminase (AID)-dependent somatic hypermutation (SHM) and CSR, and altogether behaves as a strong super-enhancer...
January 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28077417/aid-is-a-key-regulator-of-myeloid-erythroid-differentiation-and-dna-methylation-in-hematopoietic-stem-progenitor-cells
#12
Hiroyoshi Kunimoto, Anna Sophia McKenney, Cem Meydan, Kaitlyn Shank, Abbas Nazir, Franck Rapaport, Benjamin Durham, Francine E Garrett-Bakelman, Elodie Pronier, Alan H Shih, Ari Melnick, Jayanta Chaudhuri, Ross L Levine
Recent studies have reported activation-induced cytidine deaminase (AID) and ten-eleven-translocation (TET) family members regulate active DNA demethylation. Genetic alterations of TET2 occur in myeloid malignancies and hematopoietic specific loss of Tet2 induces aberrant hematopoietic stem cell (HSC) self-renewal/differentiation, implicating TET2 as a master regulator of normal and malignant hematopoiesis. Despite the functional link between AID and TET in epigenetic gene regulation, the role of AID loss in hematopoiesis and myeloid transformation remains to be investigated...
January 11, 2017: Blood
https://www.readbyqxmd.com/read/28074830/tet1-in-nucleus-accumbens-opposes-depression-and-anxiety-like-behaviors
#13
Jian Feng, Catherine J Pena, Immanuel Purushothaman, Olivia Engmann, Deena Walker, Amber N Brown, Orna Issler, Marie Doyle, Eileen Harrigan, Ezekiell Mouzon, Vincent Vialou, Li Shen, Meelad M Dawlaty, Rudolf Jaenisch, Eric J Nestler
Depression is a leading cause of disease burden, yet current therapies fully treat <50% of affected individuals. Increasing evidence implicates epigenetic mechanisms in depression and antidepressant action. Here, we examined a possible role for the DNA dioxygenase, ten eleven translocation protein 1 (TET1), in depression-related behavioral abnormalities. We applied chronic social defeat stress, an ethologically validated mouse model of depression-like behaviors, and examined Tet1 expression changes in nucleus accumbens (NAc), a key brain reward region...
January 11, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28057769/extra-nuclear-effects-of-estrogen-on-cortical-bone-in-males-require-er%C3%AE-af-1
#14
H H Farman, J Wu, K L Gustafsson, S H Windahl, S H Kim, J A Katzenellenbogen, C Ohlsson, M K Lagerquist
Estradiol (E2) signaling via estrogen receptor alpha (ERα) is important for the male skeleton as demonstrated by ERα inactivation in both mice and man. ERα mediates estrogenic effects not only by translocating to the nucleus and affecting gene transcription but also by extra-nuclear actions e.g., triggering cytoplasmic signaling cascades. ERα contains various domains, and the role of activation function 1 (ERαAF-1) is known to be tissue specific. The aim of this study was to determine the importance of extra-nuclear estrogen effects for the skeleton in males and to determine the role of ERαAF-1 for mediating these effects...
February 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/28056337/marked-enteropathy-in-an-accelerated-macaque-model-of-aids
#15
Joshua D Croteau, Elizabeth L Engle, Suzanne E Queen, Erin N Shirk, M Christine Zink
Enteropathy in HIV infection is not eliminated with combination antiretroviral therapy and is possibly linked to microbial translocation. We used a rapidly progressing SIV/pigtailed macaque model of HIV to examine enteropathy and microbial translocation. Histologic evidence of intestinal disease was observed in only half of infected macaques during late-stage infection (LSI). Combination antiretroviral therapy initiated during acute infection prevented intestinal disease. In the ileum and colon, enteropathy was associated with increased caspase-3 staining, decreased CD3(+) T cells, and increased SIV-infected cells...
January 2, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/27998928/the-cell-cycle-restricts-activation-induced-cytidine-deaminase-activity-to-early-g1
#16
Qiao Wang, Kyong-Rim Kieffer-Kwon, Thiago Y Oliveira, Christian T Mayer, Kaihui Yao, Joy Pai, Zhen Cao, Marei Dose, Rafael Casellas, Mila Jankovic, Michel C Nussenzweig, Davide F Robbiani
Activation-induced cytidine deaminase (AID) converts cytosine into uracil to initiate somatic hypermutation (SHM) and class switch recombination (CSR) of antibody genes. In addition, this enzyme produces DNA lesions at off-target sites that lead to mutations and chromosome translocations. However, AID is mostly cytoplasmic, and how and exactly when it accesses nuclear DNA remains enigmatic. Here, we show that AID is transiently in spatial contact with genomic DNA from the time the nuclear membrane breaks down in prometaphase until early G1, when it is actively exported into the cytoplasm...
January 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27986871/hiv-infection-of-kupffer-cells-results-in-an-amplified-proinflammatory-response-to-lps
#17
Arevik Mosoian, Lumin Zhang, Feng Hong, Francesc Cunyat, Adeeb Rahman, Riti Bhalla, Ankur Panchal, Yedidya Saiman, M Isabel Fiel, Sander Florman, Sasan Roayaie, Myron Schwartz, Andrea Branch, Mario Stevenson, Meena B Bansal
End-stage liver disease is a common cause of non-AIDS-related mortality in HIV(+) patients, despite effective anti-retroviral therapies (ARTs). HIV-1 infection causes gut CD4 depletion and is thought to contribute to increased gut permeability, bacterial translocation, and immune activation. Microbial products drain from the gut into the liver via the portal vein where Kupffer cells (KCs), the resident liver macrophage, clear translocated microbial products. As bacterial translocation is implicated in fibrogenesis in HIV patients through unclear mechanisms, we tested the hypothesis that HIV infection of KCs alters their response to LPS in a TLR4-dependent manner...
December 16, 2016: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/27981746/galectin-3-promotes-caspase-independent-cell-death-of-hiv-1-infected-macrophages
#18
Jing Xue, Chunyan Fu, Zhe Cong, Lingjuan Peng, Zhuoying Peng, Ting Chen, Wei Wang, Hong Jiang, Qiang Wei, Chuan Qin
HIV-1-infected macrophages are a key contributor to the formation of a viral reservoir and new treatment strategies focus on eliminating this pool of virus. Galectin-3 is a potent apoptosis-inducing protein that regulates diverse cellular activities. In the present study, we investigated whether galectin-3 could induce cell death in HIV-1-infected macrophages using HIV-1-infected THP1 monocytes (THP1-MNs) and THP1-derived macrophages (THP1-MΦs) as in vitro cellular models. We found that THP1-MΦs were more resistant than the THP1-MNs to HIV-1 infection-induced death, and that HIV-1 infection of the THP1-MΦs increased expression of the anti-apoptotic proteins Mcl-1, Bcl-2 and Bcl-xL...
November 7, 2016: FEBS Journal
https://www.readbyqxmd.com/read/27980783/plasmodium-chabaudi-infection-induces-aid-expression-in-transitional-and-marginal-zone-b-cells
#19
Joel R Wilmore, Alexander C Maue, Rosemary Rochford
INTRODUCTION: Endemic Burkitt's lymphoma (eBL) is associated with Epstein-Barr virus and repeated malaria infections. A defining feature of eBL is the translocation of the c-myc oncogene to the control of the immunoglobulin promoter. Activation-induced cytidine deaminase (AID) has been shown to be critical for this translocation. Malaria infection induces AID in germinal center B cells, but whether malaria infection more broadly affects AID activation in extrafollicular B cells is unknown...
December 2016: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/27934922/extreme-activity-of-drug-nanocrystals-coated-with-a-layer-of-non-covalent-polymers-from-self-assembled-boric-acid
#20
Honglei Zhan, Jun F Liang
Non-covalent polymers have remarkable advantages over synthetic polymers for wide biomedical applications. In this study, non-covalent polymers from self-assembled boric acid were used as the capping reagent to replace synthetic polymers in drug crystallization. Under acidic pH, boric acid self-assembled on the surface of drug nanocrystals to form polymers with network-like structures held together by hydrogen bonds. Coating driven by boric acid self-assembly had negligible effects on drug crystallinity and structure but resulted in drug nanocrystals with excellent dispersion properties that aided in the formation of a more stable suspension...
December 9, 2016: Scientific Reports
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